Psychotherapy Effects on Reward Processing in PTSD

PTSD Clinical Trial

— PERPP  

Official title:

The Effects of Trauma-focused Psychotherapy on Reward Circuitry Function and Information Encoding

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06096740
• Other study ID #: STUDY00004746
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: May 1, 2029

Study information

• Verified date: May 2024
• Source: University of Texas at Austin
• Contact: Lauren Enten, B.S.A
• Phone: 512-495-5856
• Email: fonzolab[@]austin.utexas.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to identify how trauma-focused psychotherapy changes the function of brain circuitry in posttraumatic stress disorder (PTSD) and how this mediates improvements in the diminished ability to experience positive emotions following a traumatic or extremely stressful life event. In this instance, the investigators will be using cognitive processing therapy (CPT), a widely-utilized and evidence-based treatment for PTSD.

Description:

The goals of the study are as follows:

1. Quantify, under conditions of safety (no threat), how PTSD psychotherapy alters reward circuit function and information encoding. Hypothesis: Under conditions of safety, treatment will enhance vmPFC ExpVal encoding, enhance VS encoding of PE, and decrease amygdala encoding of PE.

2. Identify how presence of threat augments PTSD psychotherapy effects on reward circuit function and information encoding. Hypothesis: In presence of threat vs. no threat, treatment will attenuate vmPFC ExpVal encoding, attenuate VS encoding of PE, and increase dorsolateral prefrontal cortex encoding of PE.

3. (Exploratory). Identify how, following psychotherapy, changes in reward circuit function and information encoding under conditions of safety and threat are associated with improvements in symptoms of diminished positive affect (DimPA).

To accomplish the goals of the study, the investigators propose a neuroimaging-coupled, randomized clinical trial of immediate vs. delayed individual cognitive processing therapy (CPT) in individuals (N=120) with a primary diagnosis of chronic PTSD. The investigators are choosing to focus on the syndromic diagnosis of PTSD in this study vs. DimPA in PTP more generally (which also frequently encompasses MDD as a diagnosis), because: a) trauma-focused psychotherapy has been validated on the syndromic diagnosis of PTSD; and b) providing this treatment to individuals without a PTSD diagnosis may diminish efficacy of the treatment in this sample, obscure detection of therapeutic mechanisms, and may not be clinically advantageous to the participant. Note that large sample-studies indicate that ~75% of individuals with a PTSD diagnosis have at least one symptom of DimPA (i.e. Emotional Numbing). Therefore, a diagnostic inclusion criterion is most likely to result in a maximally generalizable sample that will also be sensitive to CPT therapeutic effects. Individuals will undergo, prior to randomization, clinical and neurobiological assessment with fMRI during completion of several reward processing paradigms. Two of these involve both a normal "safe" context and a threat context manipulation (threat of mild electrodermal shock that is periodically cycled throughout the task). Another paradigm involves making decisions to either approach reward or forego a reward when this decision conflicts with the likelihood of an aversive outcome. This is known as approach-avoidance conflict (AAC). Finally, the investigators will incorporate a paradigm to assess emotion regulation in order to determine how this major aspect of CPT (cognitive reappraisal) relates to changes in reward circuitry function. This battery will provide a comprehensive characterization of reward processing behavior and circuit function and establish its relationship to treatment processes, as well as how such processes may vary as a function of threat.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: May 1, 2029
• Est. primary completion date: March 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• English as primary language, and comprehension suitable to understand experimenter instructions.

• Current and chronic syndromic PTSD, defined as being exposed to a DSM-5 Criterion A traumatic event, with the presence DSM-5 qualifying PTSD symptoms for at least 3 months, as assessed by the Clinician-Administered PTSD Scale for DSM-5.

• Able and willing to undergo functional magnetic resonance imaging (fMRI).

• Willingness to participate in repeated assessments and as part of a delayed treatment group.

Exclusion Criteria:

• Evidence of current or prior history of psychosis or bipolar disorder as evidenced by self-report or clinical interview.

• Active substance dependence within the past 6 months as evidenced by clinical interview.

• Current regular psychiatric medication use (i.e. antidepressants), except for as-needed benzodiazepine or opiate medication no more than three times per week, on average, or for short-duration stimulant medication for ADHD that can be skipped within 24 hours of study visits.

• A recent (<6 months) suicide attempt or current active ideation with intent.

• Unremovable ferrous metal in body.

• History of neurological disorder, stroke, seizures/convulsions (except febrile seizures in childhood), epilepsy, brain surgery, electroconvulsive or radiation treatment, brain hemorrhage or tumor, or thyroid disorder.

• Anyone who is pregnant or trying to become pregnant.

• Current or past year (> 3 sessions), psychotherapy with a prominent exposure or cognitive restructuring component (i.e. EMDR, CBT, DBT, etc.).

• Previous or current (es)Ketamine treatment and/ or brain stimulation/neuromodulatory treatment (i.e. rTMS, DBS, ECT, etc.).

• Other ongoing treatment that is likely to confound experimental effects.

• Previous penetrating head injury/TBI. Mild-to-moderate TBI without penetrating injury is allowable.

Related Conditions & MeSH terms

• Anhedonia
• Chronic Post-Traumatic Stress Disorder
• Post Traumatic Stress Disorder
• PTSD
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Behavioral:
• Cognitive Processing Therapy
Cognitive processing therapy is a widely-utilized, empirically-supported treatment developed for PTSD. It is based on a cognitive theory of trauma which emphasizes the impact of trauma on belief systems and the development of "stuck points", which are unhealthy, unrealistic, and maladaptive ways of thinking that serve to maintain unhealthy beliefs and reinforce PTSD symptoms.

Locations

Country	Name	City	State
United States	Health Discovery Building (HDB), 1601 Trinity St., Bldg B., Z0600	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas at Austin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Within subject beta coefficients for each parametrically modulated regressor of the Reinforcement Learning Task with Threat	A 6 mm sphere will be drawn around each participant's spatially normalized image at coordinates defined by prior findings in the pilot sample and average percent signal changes will serve as each individual's dependent measure.	[10 weeks]
Secondary	Within-subject BOLD contrast for unexpected absence of juice vs. expected absence of juice (negative temporal Prediction Errors).	The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation between the unexpected absence of juice vs. expected absence of juice.	[10 weeks]
Secondary	Within-subject BOLD contrast for the unexpected delivery of juice vs. the expected delivery of juice (positive temporal Prediction Errors).	The changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation between the unexpected delivery of juice vs. the expected delivery of juice.	[10 weeks]
Secondary	BOLD contrast of DECREASE Negative vs. LOOK Negative of the Cognitive Reappraisal Task.	A method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time.	[10 weeks]
Secondary	BOLD contrast of LOOK Negative vs. LOOK Neutral of the Cognitive Reappraisal Task.	A method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time.	[10 weeks]